2.1 Leukemia
Leukemia, which is the uncontrolled proliferation of blood cells, constitutes about 2% of adult cancers. The incidence rate is 2.5 out of 100,000 people. Each year, nearly 27,000 adults and more than 2,000 children in the United States are diagnosed with leukemia. In most types of leukemia, the abnormal cells are white blood cells. The leukemia cells usually look different from normal blood cells, and they do not function properly.
People with leukemia have a weakened immune system. They often get infections and have fevers. Also, people with leukemia often have less than the normal amount of healthy red blood cells and platelets. As a result, there are not enough red blood cells to carry oxygen through the body (a condition called anemia) and the patients look pale and are often weak and tired. Other common symptoms of leukemia include loss of appetite, loss of weight, swollen or tender lymph nodes, liver, or spleen, easy bleeding or bruising, tiny red spots (called petechiae) under the skin, swollen or bleeding gums, sweating (especially at night), and bone or joint pain. Because the abnormal cells may gradually collect in various parts of the body (e.g., the central nervous system, the digestive tract, kidneys, lungs, eyes, etc.), leukemia may cause nonspecific signs of headaches, vomiting, confusion, loss of muscle control, and seizures. The most efficient way to diagnose leukemia is by blood test (CBC or WBC). Bone marrow aspiration also shows evidence of leukemia cells.
The cause of leukemia is unknown. However, radiation, some toxins such as benzene, and some chemotherapy agents (drugs known as alkylating agents) used in patients treated for Hodgkin's disease, multiple myeloma, breast, ovarian, and gastrointestinal cancers are thought to cause leukemia. Abnormalities in chromosomes may also play a role in the development of acute leukemia. Immunosuppression following organ transplantation, and blood disorders such as polycythemia vera, essential thrombocythemia, and refractory anemia are also highly associated with the occurrence of leukemia.
Leukemia is either acute or chronic. In acute leukemia, the abnormal blood cells are immature cells that remain very immature and cannot carry out their normal functions. The number of blasts increases rapidly, and the disease gets worse quickly. In chronic leukemia, some blast cells are present, but in general, these cells are more mature and can carry out some of their normal functions. Also, the number of blasts increases less rapidly than in acute leukemia. As a result, chronic leukemia gets worse gradually. Leukemia can arise in either of the two main types of white blood cells—lymphoid cells (lymphocytic leukemia) or myeloid cells (myeloid or myelogenous leukemia). The most common types of leukemia are (1) acute lymphocytic leukemia (ALL), (2) acute myeloid leukemia (AML), (3) chronic lymphocytic leukemia (CLL), (4) chronic myeloid leukemia (CML), and (5) hairy cell leukemia. The French-American-British (FAB) classification divides leukemia based on morphologic, histochemical, and immunologic findings.
Treatment for leukemia is complex. Treatment of leukemia depends on the type of leukemia, the stage, the extent of the disease, whether the leukemia has been treated before, and also the age, symptoms and general health of the patient. Most people with leukemia are treated with chemotherapy. Some may also choose to have radiation therapy and/or bone marrow transplantation (BMT) or biological therapy. In some cases, surgery to remove the spleen (an operation called a splenectomy) may be part of the treatment plan. In addition, supportive care is often included by isolating patients to prevent invention, giving antibiotics to treat infection, and transfusing patients to control bleeding and red blood cells to combat anemia.
Radiation has not been highly effective as the primary treatment for leukemia, though it has been used as palliative therapy for patients with stage IV leukemia in an effort to relieve symptoms caused by the tumor. In addition, it has been on patients without metastasis following surgical removal of the primary tumor within the leukemia when the surgical margins are positive for tumor involvement, or if there is known residual tumor following surgery. Radiation is also used to shrink an especially large tumor prior to surgery or to slow the growth of inoperable tumors using either external beam (similar to an x-ray) or brachytherapy (internal radiation delivered with implanted radioactive seeds). It is common for the skin in the treated area to become red, dry, tender, and itchy. Radiation to the leukemia and nearby areas may cause nausea, vomiting, diarrhea, or urinary discomfort. Furthermore, it also dramatically reduces the meager number of healthy white blood cells left in the system.
In order to help restore the patient's immune system, a bone marrow transplant can help the patient produce enough white blood cells, red blood cells, and platelets. However, the donated bone marrow must match the patient's tissue type. Although there are many donor programs, usually a brother or a sister is the best source for so-called allogeneic BMT.
Many types of chemotherapy medications have been used for leukemia in various combinations in the past but some types of leukemia are highly resistant to chemotherapy. For instance, cytosine arabinoside (ARA-C) and anthracyclines (e.g., daunarubicin) yield response rates of 60% to 80%. Unfortunately, chemotherapy alone only cures 20% to 30% of the patients. Further, approximately 75% of patients achieving complete remission will relapse usually within 2 years. Potential side effects include nausea and vomiting, loss of hair, low blood cell counts, and fatigue. Many chemotherapeutic drugs have been tried in the past as single agents for the palliation of leukemia, but the results were generally disappointing. Nevertheless, the role of chemotherapy in the management of leukemia is continually evolving. Oftentimes, chemotherapy with radiation in adjunct to surgery is used. In general, chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease (Ali et al., 2000, Oncology 14(8):1223–30). Unfortunately, the high initial response rates to first line chemotherapy does not appear to translate into a survival benefit (Kohno and Kitahara, 2001, Gan To Kagaku Ryoho 28(4):448–53). Moreover, there are many undesirable side effects associated with chemotherapy such as temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells that may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells that may lower resistance to infection), thrombocytopenia (decreased numbers of platelets that may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea. Active chemotherapeutic agents include amsacrine (AMSA), busulfan (Myleran®), chlorambucil (Leukeran®), cladribine (2-chlorodeoxyadenosine; “2-CDA”; Leustatin®), cyclophosphamide (Cytoxan®), cytarabine (ara-C;Cytosar-U®), daunorubicin (Cerubidine®), doxorubicin (Adriamycin®), etoposide (VePesid®), fludarabine phosphate (Fludara®), hydroxyurea (Hydrea®), idarubicin (Idamycin®), L-asparaginase (Elspar®), methotrexate sodium plus 6-mercaptopurine (6-MP; Purinethol®), mitoxantrone (Novantrone®), pentostatin (2-deoxycoformycin; “DCF”; Nipent®), prednisone, retinoic acid (ATRA), vincristine sulfate (Oncovin®), and 6-thioguanine (Tabloid®).
The identification of active chemotherapeutic agents against cancers traditionally involved the use of various animal models of cancer. The mouse has been one of the most informative and productive experimental system for studying carcinogenesis (Sills et al., 2001, Toxicol Letters 120:187–198), cancer therapy (Malkinson, 2001, Lung Cancer 32(3):265–279; Hoffman R M., 1999, Invest New Drugs 17(4):343–359), and cancer chemoprevention (Yun, 1999, Annals NY Acad Sci. 889:157–192). Cancer research started with transplanted tumors in animals which provided reproducible and controllable materials for investigation. Pieces of primary animal tumors, cell suspensions made from these tumors, and immortal cell lines established from these tumor cells propagate when transplanted to animals of the same species.
To transplant human cancer to an animal and to prevent its destruction by rejection, the immune system of the animal are compromised. While originally accomplished by irradiation, thymectomy, and application of steroids to eliminate acquired immunity, nude mice that are athymic congenitally have been used as recipients of a variety of human tumors (Rygaard, 1983, in 13th International Cancer Congress Part C, Biology of Cancer (2), pp37–44, Alan R. Liss, Inc., NY; Fergusson and Smith, 1987, Thorax, 42:753–758). While the athymic nude mouse model provides useful models to study a large number of human tumors in vivo, it does not develop spontaneous metastases and are not suitable for all types of tumors. Next, the severe combined immunodeficient (SCID) mice is developed in which the acquired immune system is completely disabled by a genetic mutation. Human lung cancer was first used to demonstrate the successful engraftment of a human cancer in the SCID mouse model (Reddy S., 1987, Cancer Res. 47(9):2456–2460). Subsequently, the SCID mouse model have been shown to allow disseminated metastatic growths for a number of human tumors, particularly hematologic disorders and malignant melanoma (Mueller and Reisfeld, 1991, Cancer Metastasis Rev. 10(3):193–200; Bankert et al., 2001, Trends Immunol. 22:386–393). With the recent advent of transgenic technology, the mouse genome has become the primary mammalian genetic model for the study of cancer (Resor et al., 2001, Human Molec Genet. 10:669–675).
While surgery, chemotherapeutic agents and radiation are useful in the treatment of leukemia, there is a continued need to find better treatment modalities and approaches to manage the disease that are more effective and less toxic, especially when clinical oncologists are giving increased attention to the quality of life of cancer patients. The present invention provides an alternative approach to cancer therapy and management of the disease by using an oral composition comprising yeasts.
2.2 Yeast-Based Compositions
Yeasts and components thereof have been developed to be used as dietary supplement or pharmaceuticals. However, none of the prior methods uses yeast cells which have been cultured in an electromagnetic field to produce a product that has an anti-cancer effect. The following are some examples of prior uses of yeast cells and components thereof:
U.S. Pat. No. 6,197,295 discloses a selenium-enriched dried yeast product which can be used as dietary supplement. The yeast strain Saccharomyces boulardii sequela PY 31 (ATCC 74366) is cultured in the presence of selenium salts and contains 300 to about 6,000 ppm intracellular selenium. Methods for reducing tumor cell growth by administration of the selenium yeast product in combination with chemotherapeutic agents is also disclosed.
U.S. Pat. No. 6,143,731 discloses a dietary additive containing whole β-glucans derived from yeast, which when administered to animals and humans, provide a source of fiber in the diet, a fecal bulking agent, a source of short chain fatty acids, reduce cholesterol and LDL, and raises HDL levels.
U.S. Pat. No. 5,504,079 discloses a method of stimulating an immune response in a subject utilizing modified yeast glucans which have enhanced immunobiologic activity. The modified glucans are prepared from the cell wall of Saccharomyces yeasts, and can be administered in a variety of routes including, for example, the oral, intravenous, subcutaneous, topical, and intranasal route.
U.S. Pat. No. 4,348,483 discloses a process for preparing a chromium yeast product which has a high intracellular chromium content. The process comprises allowing the yeast cells to absorb chromium under a controlled acidic pH and, thereafter inducing the yeast cells to grow by adding nutrients. The yeast cells are dried and used as a dietary supplement.
Citation of documents herein is not intended as an admission that any of the documents cited herein is pertinent prior art, or an admission that the cited documents are considered material to the patentability of the claims of the present application. All statements as to the date or representations as to the contents of these documents are based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.